Research Details:

    What is angiogenesis?

It is the process of new capillary growth from those pre-existing. Capillaries are the smallest blood vessels and are the sites of nutrient and gas exchange between the vascular system and the surrounding organs. Capillaries are composed of a single layer of endothelial cells that are surrounded by a layer of extracellular matrix (basement membrane) that provides structural support and attachment sites for the endothelial cells.

Exercise training, and other situations that cause chronic increases in energy and oxygen demand, stimulates the growth of additional capillaries so that oxygen delivery is enhanced. This is a complex multi-step process involving endothelial cell activation, proliferation and the production of proteases that clip holes in the basement membrane. Endothelial cells then can migrate away from the pre-existing capillary into the surrounding tissue, where they will establish a new capillary branch that connects with a neighbouring capillary.

Cross-section of skeletal muscle
                     Labeled with a protein that outlines muscle cells and capillaries
                     More capillaries surrounding muscle fibers means better muscle endurance and improved health.
                     What determines the number of capillaries around muscle fibers, and how can we increase this number?

 

    How do we study angiogenesis?

We isolate endothelial cells from skeletal muscle and culture these cells under conditions that allow them to form networks similar to the process of capillary growth.

We can then analyze gene expression and the role of specific signalling pathways required for the initiation of endothelial cell network formation.

In particular, we analyze the regulation of matrix metalloproteinases MMP-2 and MT1-MMP.
 

This figure shows skeletal muscle microvascular endothelial cells cultured in a three-dimensional collagen matrix. The cells elongate and form network connections with other endothelial cells in the matrix.